Enhancing Microglial Myelin Repair Mechanisms through Stimulation of the Ppar-Delta Nuclear Receptor as a Novel Therapeutic Approach for Multiple Sclerosis

Background: Myelin, the protective coating surrounding nerve fibres, is necessary for the transmission of nerve impulses in the body. In people with multiple sclerosis (MS), the immune system attacks myelin, causing inflammation and often damaging the myelin coating. The brain possesses the capacity for repairing myelin, however, patients with primary progressive multiple sclerosis or relapsing-remitting MS invariably accumulate extensive myelin and nerve cell damage that lead to the development of significant disability burden.

Overview: Evidence suggests that over time the brain becomes increasingly ineffective at eliminating myelin debris that are liberated as part of the MS pathology. This is significant, because it contributes to disease progression, as these debris must be eliminated to allow for the brain’s natural ability to repair myelin. In the brain, cells called ‘microglial’ cells mediate debris clearance. This work, led by Dr. David Gosselin, will study how nuclear receptor Ppar-delta (Pparδ) regulates this function in microglial. The researchers will also attempt to stimulate Ppar-deltav(Pparδ) with drugs to enhance myelin clearance by microglia.

Impact: This study hopes to unravel a novel mechanism of myelin repair one that regulates microglial debris elimination and inflammatory activity to offer new therapeutic options for people living with MS.

Project Status: In Progress